rs998707315

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001199107.2(TBC1D24):​c.-116+3G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)

Consequence

TBC1D24
NM_001199107.2 splice_region, intron

Scores

2
Splicing: ADA: 0.2275
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.509
Variant links:
Genes affected
TBC1D24 (HGNC:29203): (TBC1 domain family member 24) This gene encodes a protein with a conserved domain, referred to as the TBC domain, characteristic of proteins which interact with GTPases. TBC domain proteins may serve as GTPase-activating proteins for a particular group of GTPases, the Rab (Ras-related proteins in brain) small GTPases which are involved in the regulation of membrane trafficking. Mutations in this gene are associated with familial infantile myoclonic epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBC1D24NM_001199107.2 linkc.-116+3G>C splice_region_variant, intron_variant Intron 1 of 7 ENST00000646147.1 NP_001186036.1 Q9ULP9-1
TBC1D24NM_020705.3 linkc.-116+3G>C splice_region_variant, intron_variant Intron 1 of 6 NP_065756.1 Q9ULP9-2
TBC1D24XM_017023493.2 linkc.-116+3G>C splice_region_variant, intron_variant Intron 1 of 8 XP_016878982.1 Q9ULP9-1
TBC1D24XM_017023495.2 linkc.-116+3G>C splice_region_variant, intron_variant Intron 1 of 7 XP_016878984.1 Q9ULP9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBC1D24ENST00000646147.1 linkc.-116+3G>C splice_region_variant, intron_variant Intron 1 of 7 NM_001199107.2 ENSP00000494678.1 Q9ULP9-1
TBC1D24ENST00000567020.6 linkc.-116+3G>C splice_region_variant, intron_variant Intron 1 of 6 1 ENSP00000454408.1 Q9ULP9-2
TBC1D24ENST00000569874.2 linkn.-116+3G>C splice_region_variant, intron_variant Intron 1 of 7 5 ENSP00000455005.2 Q9ULP9-2
TBC1D24ENST00000630263.2 linkn.-142+3G>C splice_region_variant, intron_variant Intron 1 of 7 5 ENSP00000486835.1 A0A0D9SFR5

Frequencies

GnomAD3 genomes
AF:
0.00000670
AC:
1
AN:
149204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
0
GnomAD4 genome
AF:
0.00000670
AC:
1
AN:
149204
Hom.:
0
Cov.:
33
AF XY:
0.0000138
AC XY:
1
AN XY:
72702
show subpopulations
Gnomad4 AFR
AF:
0.0000243
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
17
DANN
Benign
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.23
dbscSNV1_RF
Benign
0.55
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.32
Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs998707315; hg19: chr16-2525174; API